The Polymerase Chain Reaction (PCR) is one of the most widely used techniques in molecular biology. In general, most thermocyclers rely upon programmable heat blocks which have a large thermal mass consequently, most of the time in a PCR cycle is spent non-productively in transition between denaturation, annealing, and elongation temperatures. Recently, much faster hot-air thermocyclers have been constructed which shorten these transition times, allowing 30 cycles of PCR in 10 to 30 minutes. While elegant in principle, the design of these systems is not optimal. Air is a relatively poor heat transfer medium, and the operation of a single heat/reaction chamber at atmospheric pressure is inherently slow. Much faster thermocyclers can be constructed using pressurized helium gas delivered to a reaction chamber by computer-controlled electronic valves. In Phase I Research, a pressurized helium gas thermocycler will be fabricated and tested. Performance will be demonstrated by amplification o f an 85 b.p. human platelet antigen (HPA-4) amplicon and a 107 b.p. E. coli 0157:H7 uidA amplicon. These experiments will demonstrate the feasibility of using rapid gas phase PCR for high-throughput-screening (HTS) diagnostics of heritable and infectious disease in less than one minute. PROPOSED COMMERCIAL APPLICATIONS: The proposed method is 10 times faster than the fastest commercially available hot-air PCR thermocyclers; and 100 times faster than commonly used heat block thermocyclers. Phase I Research will develop enabling technology for high-throughput-screening (HTS) capabilities, which can be applied to diagnostics, drug discovery, and functional genomics related to heritable and infectious diseases. There is large and growing market for high-speed PCR for medical/veterinary diagnostics and biomedical research.